2-Deoxy-d-Glucose (2-DG)-Induced Cardiac Toxicity in Rat: NT-proBNP and BNP as Potential Early Cardiac Safety Biomarkers.

2-Deoxy-d-glucose (2-DG) is being developed as a potential anticonvulsant and disease-modifying agent for patients with epilepsy; however, during preclinical development, cardiac toxicity has been encountered in rats. This study was performed to determine whether cardiac troponin (cTnI and cTnT), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and/or creatine kinase (CK) could be useful as indicators of 2-DG cardiac toxicity. In addition, this study also investigated the association of cardiac histopathological changes with these biomarkers. F344 rats (4/sex/group/sacrifice point) were gavaged with either vehicle or 2-DG (50, 125, or 375 mg/kg twice daily; total daily dose of 100, 250, or 750 mg/kg/d) for 7, 14, 21, or 45 days followed by a 15-day recovery. Dose-dependent increases in NT-proBNP and BNP plasma concentrations were observed. Following recovery period, the NT-proBNP and BNP concentrations returned to baseline levels. There were no remarkable increases in CK, ANP, cTnI, or cTnT concentrations. There were no gross cardiac lesions observed at the necropsy. Microscopic findings of vacuolar degeneration and hypertrophy of the endothelial cells of the endocardium were present in the heart at doses of 250 and 750 mg/kg/d. Microscopic findings, in general, were associated with increases in NT-proBNP levels. Cardiac toxicity appeared to be reversible. In conclusion, NT-proBNP and BNP are potential early biomarkers for 2-DG-induced cardiac toxicity that can be useful to monitor 2-DG therapy in clinical trials.

Gastric adenocarcinoma in a horse with portal vein metastasis and thrombosis: a novel cause of hepatic encephalopathy.

A 17-year-old Quarter horse mare was referred to Cornell University for postmortem examination after 72 hours of encephalopathy that consisted of depression, mania, and blindness. A plasma sample and cerebral spinal fluid demonstrated hyperammonemia. Gross necropsy examination findings included the following: mild icterus, a transmural mass in the glandular portion of the gastric fundus, multiple masses throughout the liver, and a large tumor thrombus in the portal vein. Microscopically, the gastric mass, hepatic masses, and portal vein thrombus were composed of similar neoplastic epithelial cells that formed variably sized acini and branching cords separated by a dense desmoplastic stroma. Throughout the cerebral frontal cortex were numerous Alzheimer type II astrocytes. Hepatic encephalopathy was caused by gastric adenocarcinoma, with metastasis to the liver and the portal vein. The clinical and pathologic lesions from this unique case, as well as hyperammonemia and portal vein thrombosis in the pathogenesis of hepatic encephalopathy, are discussed.

Feline systemic reactive angioendotheliomatosis: eight cases and literature review.

A rare, multisystemic intravascular proliferative disorder was identified postmortem in eight cats. The majority of these cats died or were euthanized following episodes of dyspnea, lethargy, and anorexia. Microscopic examination revealed occlusive, intraluminal proliferations of spindle cells within small vessels. The heart was consistently involved, and myocardial dysfunction was the probable cause of illness in all cats. Immunohistochemically, the majority of intravascular cells expressed von Willebrand factor, and a smaller number expressed smooth muscle actin, compatible with a dual population of endothelial cells and pericytes, suggesting a reactive rather than a neoplastic process. Four cases of a similar feline vascular disorder from the veterinary literature are reviewed. The histopathology resembles reactive angioendotheliomatosis in humans, a benign cutaneous intravascular endothelial and pericytic proliferative condition. However, in contrast, this feline disease is multisystemic and fatal. We propose the name "feline systemic reactive angioendotheliomatosis" for this unique, idiopathic disorder of domestic cats.

The impostor phenomenon: self-perceptions, reflected appraisals, and interpersonal strategies.

Three studies tested theoretical assumptions regarding the impostor phenomenon. In Study 1, participants completed measures of impostorism, rated themselves, and indicated how they thought other people regarded them. Contrary to standard conceptualizations of impostorism, high impostors were characterized by a combination of low self-appraisals and low reflected appraisals. Study 2 was an experiment designed to determine whether the behaviors associated with the impostor phenomenon are interpersonal strategies. Participants were told that they were expected to perform either better or worse than they had previously predicted on an upcoming test, then expressed their reactions anonymously or publicly. High impostors expressed lower performance expectations than low impostors only when their responses were public. When expectations for performance were low, participants high in impostorism responded differently under public than private conditions. Study 3 examined the possibility that high scores on measures of impostorism may reflect two types of impostors--true impostors (who believe that others perceive them too positively) and strategic impostors (who only claim that they are not as good as other people think). The results did not support this distinction; however, evidence for the strategic nature of impostorism was again obtained. Although people may experience true feelings of impostorism, these studies suggest that the characteristics attributed to so-called impostors are partly interpersonal, self-presentational behaviors designed to minimize the implications of poor performance.